BenDao Gene Completes Series A Financing of RMB 60 Million to Propel Gene Therapy from '1 to 100'

VCBeat has learned that Shanghai Bendao Gene Technology Co., Ltd. (hereinafter referred to as “Bendao Gene”), a global leader in gene therapy development with proprietary delivery technologies, has recently successfully completed a RMB 60 million Series A financing round. The round was led by Huakong Fund, with participation from ENNOVATION VENTURESS, Longmen Capital, ETP Fund, and Inno Angel Fund, among others. Probe Capital served as the exclusive financial advisor. The proceeds will be used for preclinical and clinical development of multiple product candidates, as well as for laboratory infrastructure and team building. Previously, Bendao Gene received strategic investment from Saifu Pharmaceuticals in June 2019 and tens of millions of RMB in Pre-Series A funding from Kaixuan Venture Capital in March 2020.

According to available information, Bendao Gene, founded in 2018, is an innovative company focused on the development of in vivo gene editing and ex vivo gene therapy treatments. The company has attracted significant attention from investment institutions since its inception, securing funding from multiple investors. Why has it become a favorite among capital markets? What are its core technologies? And what competitive advantages do its leading products offer?

For hereditary, infectious, and degenerative diseases that are untreatable or difficult to treat with conventional drugs, gene therapy offers the potential for a “one-shot cure” and has emerged in recent years as the third revolutionary therapeutic modality, following small-molecule chemical drugs and antibody-based therapies.

From the initial emergence of the third-generation gene-editing technology CRISPR in 2012, to the first in vivo clinical trial of CRISPR in March 2020, and further to CRISPR being awarded the Nobel Prize in Chemistry in October 2020, these milestone events have marked the increasing maturity of gene-editing technology. However, delivery technology remains the greatest obstacle in the field of gene-editing therapeutics.

Nobel laureate Jennifer Doudna argued in a January 2020 article in Nature that “delivery remains perhaps the biggest bottleneck to somatic-cell genome editing.”

Globally, the three major platforms for gene therapy delivery that have undergone human clinical validation are adeno-associated viruses (AAV), lentiviral vectors, and nanocomposite materials. However, these platforms all exhibit certain limitations when used for gene editing delivery. An ideal gene editing delivery tool must combine transient expression with high efficiency to ensure both the safety and efficacy of the treatment.

Dr. Cai Yujia, founder of Bendao Gene, pursued his doctoral studies in gene therapy under the supervision of Professor Thomas Perlmann, a professor at the Karolinska Institute in Sweden and Secretary-General of the Nobel Committee, and Professor Jacob G. Mikkelsen at Aarhus University in Denmark. Upon returning to China, he served as a researcher at the Shanghai Institutes for Biological Sciences’ Center for Systems Biomedicine at Shanghai Jiao Tong University. He has mastered core technologies related to gene therapy vectors and possesses extensive experience in the engineered design and modification of viral vectors for gene therapy. In recent years, the company has successfully developed a clinically validated gene therapy delivery platform—VLP-mRNA (virus-like particle mRNA)—which delivers CRISPR/Cas9 mRNA to achieve safe and controllable in vivo gene editing therapies.

In early November 2020, the world’s second clinical study of in vivo CRISPR gene editing therapy was successfully completed (the first globally was completed by Feng Zhang’s team at Editas Medicine in March 2020), marking the first clinical study of CRISPR-based antiviral therapy worldwide. This delivery technology utilizes lentiviral capsids to deliver Cas9 mRNA, combining the high efficiency of viral vector cell infection (99.8% in vitro infection rate; >50% in vivo infection rate) with the transient nature of mRNA expression (degradation within 72 hours). It has demonstrated therapeutic efficacy in animal models of various diseases and offers technical advantages such as transient in vivo expression, avoidance of the long-term safety risks associated with AAV-mediated CRISPR expression, negligible off-target effects, and low immunogenicity. Currently, under the review and approval of the Ethics Committee of the Eye & ENT Hospital of Fudan University, Professor Hong Jiaxu’s team is leading an initial clinical application study to evaluate the safety and controllability of this technology. In the future, this technology will be expanded to treat other viral infections, ophthalmic diseases, and neurological disorders.

Mr. Zhang Yang, Chairman of Huakong Fund, stated that the gene therapy industry is characterized by vast market potential and exceptionally high technical barriers. While breakthroughs have been achieved in gene editing technologies, delivery systems have remained the primary bottleneck. In recent years, Dr. Cai Yujia, founder of Bendao Gene, and his team have successfully achieved a “zero-to-one” innovative breakthrough in gene editing delivery technology. For over a decade, Dr. Cai has been dedicated to developing gene therapy delivery technologies, successfully establishing multiple original delivery technology platforms, including virus-like particle (VLP)-based CRISPR/Cas9 mRNA gene editing delivery technology and next-generation lentiviral delivery technology. The company’s original therapeutic product for viral keratitis has demonstrated exceptional preclinical animal data and is currently undergoing non-registration human clinical trials at leading ophthalmology hospitals in China. The company has also established a diverse product pipeline covering gene editing therapies for hereditary, infectious, and degenerative diseases, viral vector-based treatments for blood disorders, and mRNA vaccines.

Regarding the exclusive lead investment in this Series A financing by Huakong Fund, Mr. Zhang Yang expressed his sincere gratitude to Professor Cai Yujia, founder of Bendao Gene, and existing shareholders for their trust. He stated that they will provide long-term support to the company’s development, jointly advancing Bendao Gene’s proprietary delivery technologies and products. This collaboration aims to facilitate a leap from “1 to 100” in gene therapy, ensuring that more patients with difficult-to-treat or untreatable conditions can truly benefit in the future.

Established in 2007, the firm manages over RMB 10 billion in assets through a portfolio of more than 20 subsidiary funds, including venture capital (VC), private equity (PE), industry-specific funds, merger and acquisition (M&A) funds, overseas funds, as well as specialized funds for general aviation and the military-industrial sector. Committed to becoming China’s premier private equity investment institution, it focuses on PE investments in industries such as biopharmaceuticals and high-end manufacturing, while consistently adhering to the investment strategies of “value investing” and “research-first.”“Value investing” refers to Huakong Fund’s persistent commitment to cultivating its ability to identify companies that are “on the verge of becoming great or have the potential to become great.” The fund selects leading enterprises in high-growth niche sectors and grows alongside these companies. “Research-first” entails identifying high-quality investment targets through top-down industry research. To date, the firm has completed over 50 industry research reports, scanned more than 150 niche sectors, built a pipeline of over 1,000 projects, and accumulated resources from more than 200 industry experts.The fund has already invested in more than ten leading companies in niche sectors that possess proprietary technology platforms and advanced product pipelines. Several of these portfolio companies have successfully completed initial public offerings (IPOs) or are in the process of listing on domestic or international exchanges. Moving forward, the firm aims to accelerate the growth of more outstanding healthcare enterprises.

Established in 2015, this venture capital firm specializes in the biopharmaceutical and healthcare sectors. It currently manages four equity investment funds with assets under management exceeding RMB 1.5 billion. The company’s management team and investors possess extensive investment and industry expertise in biopharma and healthcare, focusing on the commercial value generated by the integration of “Life,” “Health,” and “Innovation.”

Established in 2017, the firm specializes in equity investments in early-to-mid-stage enterprises and the incubation of startup projects, with a primary focus on innovative life sciences and medical technologies. It has launched three healthcare funds to date, and its core team possesses extensive experience in operational management and investment mergers and acquisitions within the medical sector.

Founded in 2000, the firm specializes in early-stage investments in the biopharmaceutical sector, with a particular focus on genomics. It maintains branches in Silicon Valley, Boston, Maryland, Beijing, and Wuxi. To date, it has invested in or established more than 100 companies, over 20 of which are publicly listed.·

Established in 2013, Innocore Angel Fund manages an angel fund of RMB 4 billion and has invested in over 400 innovative projects to date. Its investment management team boasts an average of more than 10 years of angel investment experience. Building upon its Tsinghua University alumni network, the firm has established a multi-dimensional startup service ecosystem. Committed to becoming a self-evolving, cross-regional, and innovative angel investment platform, Innocore Angel Fund adheres to the mission of “fostering innovation to achieve mutual success” and maintains a strong presence in major entrepreneurial hubs, including Beijing, the Yangtze River Delta, the Guangdong-Hong Kong-Macao Greater Bay Area, and Silicon Valley in the United States.

On January 11, 2021, Cai Yujia and his team publicly unveiled the world’s first virus-like particle (VLP)-mediated delivery technology for CRISPR/Cas9 mRNA in the prestigious international academic journal Nature Biotechnology. Using this technology to treat viral keratitis, they successfully eradicated the latent HSV-1 reservoir in the trigeminal ganglia in mouse models, achieving a groundbreaking “zero-to-one” innovation in gene therapy for viral keratitis.

The research findings received high praise and recognition from the reviewers at Nature Biotechnology: the results were corroborated by multiple technical approaches, eliciting rare and strong appreciation; the data quality was described as “near exceptional” and compelling, and the study was deemed to “make an excellent contribution to the field” of antiviral research.

During the same period, Cai Yujia’s team published preclinical data in *Nature Biomedical Engineering* on the use of CRISPR/Cas9 mRNA virosome delivery gene-editing technology for the treatment of wet age-related macular degeneration.

Bendao Gene’s CRISPR-Cas9 mRNA virus-like particle delivery gene editing technology has also received high recognition from top clinical experts in ophthalmology:

(1) Professor Yuan Jin, Deputy Director of the Zhongshan Ophthalmic Center at Sun Yat-sen University: The application of gene editing to the treatment of herpes simplex keratitis (HSK) undoubtedly represents a groundbreaking “zero-to-one” innovation. This study confirms that gene editing can inhibit the transport and replication of HSV in animal models of HSK, holding promise as a novel therapy for viral keratitis and addressing the clinical challenge of disease recurrence.

(2) Researcher Hong Jiaxu, Deputy Director of the Department of Ophthalmology at the Eye and ENT Hospital of Fudan University: The gene therapy industry must leverage high-quality medical expertise to drive in-depth development, and Professor Cai commands the premier ophthalmic resources in East China. The findings of this study have received extensive coverage in authoritative media outlets such as People’s Daily, and have drawn significant attention from local governments and leaders, paving the way for substantial policy support in the future.

(3) Professor Shi Weiyun, Head of the Cornea Group of the Ophthalmology Branch of the Chinese Medical Association and President of Shandong Eye Hospital: For a long time, recurrent viral keratitis has been a clinical challenge. Existing antiviral and anti-inflammatory treatments do not fundamentally address the issue of viral latency in trigeminal neurons. The original gene-editing therapeutic technology published by Professor Cai Yujia from Shanghai Jiao Tong University and Director Hong Jiaxu from Fudan University in the top international journal Nature Biotechnology provides a new approach for the radical cure of viral keratitis, which is promising.